Acetaminophen and H2O2 activate Ca2+ entry and a nonselective cation current in rat hepatocytes. (A) Ca2+ entry in hepatocytes treated with 10 mM acetaminophen for 60 min under the conditions indicated in A (average data from three separate cell preparations). Both clotrimazole (50 μM) and ACA (10 μM) were applied to the bath 5 min before the addition of Ca2+. (B) I-V plots of membrane currents measured in control hepatocytes, and hepatocytes treated with 10 mM acetaminophen for 60 min in control bath solution, after replacement of 140 mM NaCl in the bath solution with 140 mM NMDG Cl and after the addition of 50 μM clotrimazole to the bath (n = 22 for each trace). Error bars are omitted for clarity here and all other I-V plots. (C) Ca2+ entry in hepatocytes treated with 0.5 mM H2O2 (n = 3). (D) I-V plots of membrane currents measured in control hepatocytes, and hepatocytes treated with 0.5 mM H2O2 in control bath solution, after replacement of 140 mM NaCl in the bath solution with 140 mM NMDG Cl and after the addition of 50 μM clotrimazole to the bath (n = 7). (E) Activation of membrane conductance in hepatocytes by 10 mM H2O2 applied to the bath. Each data point represents amplitude of the current at −100 mV. (F) I-V plots of membrane currents measured before application of H2O2 (control), and after full development of the H2O2-activated current in control bath solution (H2O2) and after replacement of 140 mM NaCl with 140 mM NMDG Cl (n = 5).